RAF1 and melanoma: This CRAF mutation shows the critical aspects of an oncogenic driver mutation: homozygosity and highly amplified expression of this locus indicates strong positive selection pressure25; the derived melanoma cell line is strictly dependent on CRAF (R391W) expression for activity of MAPK signaling and proliferation; exogenous CRAF R391W expression strongly enhances kinase activity, homodimerization and induces downstream MAP kinase signaling; and CRAF R391W induces anchorage independent growth and can functionally replace BRAF V600E in a melanoma cell line.